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Brain γ-Glutamyltranspeptidase: Characteristics, development and thyroid hormone dependency of the enzyme in isolated microvessels and neuronal/glial cell plasma membranes

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Abstract

The characteristics, cellular locus and regulation of the enzyme γ-glutamyltranspeptidase (γGT) in brain were examined. In rat brain homogenates, the activity of the enzyme exhibited tissue differences - kidney >>>brain ==testis >>, liver >>skeletal muscle = ventricular muscle and regional differences - brain stem >hippocampus = cerebellum >cerebral cortex, with no significant species/strain differences in the select group of mammals studied. Methods were developed for the isolation from brain of microvessels (MV) and plasma membranes from neuronal/glial cells (N/G PM) utilizing morphological indicators and marker analyses. γGT activity was >12 higher in MV than N/G PM; however the enzyme displayed: stability, heat-activation and inhibition with maleate to the same extent in both fractions. A comparative study indicated that in the N/G PM fraction, γGT activity was low in all animals studied; γGT activity in MV however, was barely detectable in amphibians and reptiles, very low in birds and very high in mammal - mirroring the phylogenetic development of a functional blood-brain barrier. In the rat, γGT in both MV and N/G PM displayed a pronounced postnatal increase in activity but the extent and the patterns were different - in all cases, that of the MV greatly exceeded that of the N/G PM and in the MV, the enzyme activity exhibited same pattern as the postnatal development of the blood-brain barrier. The induction of congenital hypothyroidism by propylthiouracil (PTU) had no effect on γGT in N/G PM but effected a one third reduction in the activity of γGT in MV. The normalization by thyroid hormone replacement indicated that MV γGT is under thyroid hormone control. The induction of hypothyroidism by PTU in the adult, however, was without effect on enzyme activity in either fraction. The implications of the thyroid hormone dependency of MV γGT in the neonatal period and the relationship of & ggr;GT to the function of the blood brain-barrier is discussed.

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Authors and Affiliations

  1. Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskachewan, Canada, S7N 5E5 E-mail

    Susan Hemmings

  2. Institute of Biochemistry, Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada, K1S 5B6 E-mail

    Kenneth Storey

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  1. Susan Hemmings
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  2. Kenneth Storey
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Hemmings, S., Storey, K. Brain γ-Glutamyltranspeptidase: Characteristics, development and thyroid hormone dependency of the enzyme in isolated microvessels and neuronal/glial cell plasma membranes. Mol Cell Biochem 202, 119–130 (1999). https://doi.org/10.1023/A:1007069431615

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